Phase II, multi‑cohort trial of neoadjuvant and post‑surgery IO102‑IO103 and pembrolizumab in patients with selected resectable tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IO Biotech ApS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Sep 2023 → 29 Jan 2026

Decision date (initial)

2023-08-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

IO Biotech ApS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To investigate the efficacy of neoadjuvant treatment with IO102‑IO103 in combination with pembrolizumab, in terms of major pathological response (MPR) in resected tumors.

Secondary objectives 3

1. • To investigate the efficacy of IO102‑IO103 in combination with pembrolizumab as neoadjuvant treatment in terms of pathological complete response (pCR), pathological response rate and objective response rate (ORR)
2. • To investigate the efficacy of IO102‑IO103 in combination with pembrolizumab as neoadjuvant and post‑surgery treatment in terms of event-free survival (EFS) and disease-free survival (DFS)
3. • To investigate the safety and tolerability of IO102‑IO103 in combination with pembrolizumab as neoadjuvant and post‑surgery treatment

Conditions and MedDRA coding

Melanoma and squamous cell carcinoma of the head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
2. Candidate for surgical resection with curative intent
3. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial
4. Age ≥18 years on the day of signing the informed consent form
5. Have provided archival tumor tissue sample (≤3 months old) or newly obtained core or excisional biopsy of a tumor lesion (primary tumor and/or lymph node) not previously irradiated.
6. Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1
7. Adequate organ function
8. Women of childbearing potential: Negative urine or serum pregnancy within 72 hours prior to receiving the first dose of trial medication.
9. Women of childbearing potential: Willing to use highly effective contraception or abstain from heterosexual activity for the duration of the trial and for at least 120 days after the last dose of trial medication
10. HIV‑infected patients must be on anti‑retroviral therapy (ART) and have a well‑controlled HIV infection/disease defined as: a Patients on ART must have a CD4+ T‑cell count 350 cells/mm3 at time of screening b Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to first dose of trial medication (Day 1) c Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to first dose of trial medication (Day 1)
11. Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to start of trial intervention
12. Patients with a history of hepatitis C (HCV) infection are eligible if HCV viral load is undetectable at screening
13. Melanoma‑specific inclusion criteria: • Histologically or cytologically confirmed diagnosis of cutaneous stage III melanoma according to the American Joint Committee on Cancer (AJCC) 8th edition. Patients with resectable tumors are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal metastasis or at the time of clinically detected nodal recurrence; they may belong to any of the following groups: o Primary cutaneous melanoma with clinically apparent regional lymph node metastases o Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin o Clinically detected primary cutaneous melanoma involving multiple regional nodal groups o Clinically detected nodal melanoma (if single site) arising from an unknown primary o Relapsed resectable stage III melanoma
14. SCCHN‑specific inclusion criteria: • Newly diagnosed and histologically confirmed SCCHN that presents as locoregionally advanced (stage III or IVA) resectable disease of the oral cavity, oropharynx (with known HPV‑negative or p16‑negative status assessed per institution standard), hypopharynx, or larynx

Exclusion criteria 20

1. Currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks of the first dose of trial treatment
2. Any prior systemic treatment for the tumor under study. Melanoma patients may have received prior non-immunotherapy adjuvant therapy if more than 6 months prior to the first dose of trial treatment.
3. Prior therapy with an anti‑PD‑1, anti‑PD‑L1, or anti‑PD‑L2 agent or with an agent directed to another stimulatory or co‑inhibitory T‑cell receptor.
4. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of trial treatment
5. Live or live‑attenuated vaccine within 30 days prior to the first dose of trial treatment
6. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients who are currently receiving steroids at a dose equivalent to <5 mg/day of prednisone do not need to discontinue steroids prior to enrollment. Patients who require topical, ophthalmologic and inhalational steroids will not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjögren’s syndrome will not be excluded from the trial
7. Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
8. History of an allogeneic tissue/solid organ transplant
9. Active autoimmune disease that has required systemic treatment in past 2 years. Patients with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders not requiring systemic treatment; or conditions not expected to recur in the absence of an external trigger are permitted to enroll
10. History of radiation pneumonitis
11. History of (non‑infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
12. Active infection requiring systemic therapy
13. HIV‑infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
14. Has known active hepatitis B virus or known active hepatitis C virus (HCV) infection
15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
16. Psychiatric or substance abuse disorders that would interfere with the patient’s ability to cooperate with the trial requirements
17. Severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients
18. Women of childbearing potential: Pregnant or breastfeeding, or expecting to conceive a child within the projected duration of the trial, from time of informed consent until at least 120 days after the last dose of trial treatment
19. Melanoma‑specific exclusion criteria: • Current or prior history of uveal, mucosal, or acral melanoma • Oligometastatic stage IV melanoma • History of in‑transit or satellite metastases within the last 6 months • Prior therapy targeting BRAF and/or MEK
20. SCCHN‑specific exclusion criteria: • Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MPR, defined as pCR (0% residual viable tumor) or near pCR (≤10% residual viable tumor) at surgery (central assessment)

Secondary endpoints 6

1. pCR (0% residual viable tumor) at surgery (central assessment)
2. Pathological response rate (% of patients with pPR, near pCR or pCR) (central assessment)
3. ORR, determined by RECIST 1.1, at the end of neoadjuvant treatment (investigator assessment)
4. EFS from the start of neoadjuvant treatment (investigator assessment)
5. DFS from the date of surgery (investigator assessment)
6. Safety endpoints • Incidence of adverse events (AEs) • Incidence of serious adverse events (SAEs) • Incidence of treatment-related AEs • Incidence of treatment-related SAEs • Incidence of AEs leading to discontinuation of trial treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IO Biotech ApS

Sponsor organisation

IO Biotech ApS

Address

Ole Maaloes Vej 3

City

Copenhagen N

Postcode

2200

Country

Denmark

Scientific contact point

Organisation

IO Biotech ApS

Contact name

Shane O’Neill

Public contact point

Organisation

IO Biotech ApS

Contact name

Shane O’Neill

Third parties 8

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications